A new murine model of accelerated senescence.

Five senescence-prone series of mice (P-1, P-2, P-3, P-4 and P-5) and three senescence-resistant series (R-1, R-2 and R-3) were obtained by continuous sister-brother breeding from five original litters of AKR mice with severe deterioration, and the three original litters of AKR mice with normal aging, respectively. A grading score system was adopted to evaluate the degree of senescence of these mice and a steady and irreversible increase in this grading score was seen with advancing age in both the R and P series. The high grading score in the P series was due to an earlier onset of loss of passivity and reactivity, loss of skin glossiness and increased coarseness, hair loss, periophthalmic lesions, increased lordokyphosis of the spine and a more marked increase in their severity with advancing age as compared to the R series. Among the P series, P-2 showed a 100% incidence of systemic amyloidosis after 6 months of age and P-3 a 70% incidence of cataract over 16 months of age. The life span in the P series was shortened by about 26% of that of the R series. In view of the evidence obtained from the survivors, the growth rate and Gompertz function, the aging pattern in the P series was considered to be an acceleration of senescence. The P series has been named "SAM" ("Senescence Accelerated Mouse").